The objective of this program is the determination of threshold conditions for selected bioeffects that are expected to be sensitive indicators of damage at many levels of biological structure and function. The relationship of such threshold conditions to exposures currently being employed in ultrasonic diagnosis and therapy should be of interest to clinicians. Bioeffects will be sought within the exposure ranges of 1-10 MHz, CW and pulsed (3-100 micron sec) modes, 1-10 to the fourth power sec, 1-10 repetitive exposures, 1-10 X/cm squared. Analyses of exposed Swiss-Webster mice and tissue cultures will be performed by histochemical micro-techniques for monitoring critical metabolites, by cytological techniques for detecting toxicity and genetic instability, by optical and electron microscopy, and by observation of anomalies in reproductive physiology. A strength of this program project lies in the collaboration of four interrelated teams of basic biomedical scientists with a team of physicistsand engineers responsible for design, construction, and operation of the ultrasonic exposure equipment.